Vincamine as a
Potential Therapeutic Agent for Sickle Cell Disease: A Comprehensive Computational
Study
Basumatary Nerswn, Chetia Pankaj, Baruah Chittaranjan and Sarmah Jatin
Res. J. Biotech.; Vol. 20(3); 102-111;
doi: https://doi.org/10.25303/203rjbt1020111; (2025)
Abstract
Sickle cell disease refers to a hereditary blood condition, characterized by the
presence of abnormally shaped erythrocytes resulting from a singular point mutation
in the β-globin gene, causing various health complications. At present, hydroxyurea
remains the sole pharmacological agent for sickle cell disease management, despite
its adverse effects. This investigation examines 64 naturally occurring compounds,
documented to exhibit anti-sickling properties as alternative to hydroxyurea, using
computational techniques. In this research, molecular docking was utilized to assess
the binding affinity of 64 natural compounds with haemoglobin S, along with ADME
analysis to determine drug-likeness and pharmacokinetic profiles of the compounds,
followed by molecular dynamics and binding free energy calculations to evaluate
stability of the protein-ligand complex.
Based on the outcomes of molecular docking and ADME analysis, vincamine was identified
to possess favourable binding affinity and passed necessary pharmacokinetic criteria.
Molecular dynamics simulations and free energy assessments indicated that vincamine-HbS
complex maintained stability, exhibiting moderate flexibility and compactness. The
combined approach of molecular docking, ADME and molecular dynamics simulations
highlights vincamine as a promising candidate for the therapeutic intervention of
sickle cell disease. Additional experimental validations, both in vitro and in vivo,
are however necessary to validate the anti-sickling effectiveness of vincamine.
